Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW3LY1C)

DOT Name Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G)
Synonyms PI3K-C2-gamma; PtdIns-3-kinase C2 subunit gamma; EC 2.7.1.137; EC 2.7.1.154; Phosphoinositide 3-kinase-C2-gamma
Gene Name PIK3C2G
Related Disease
Advanced cancer ( )
Hyperlipidemia ( )
Myocardial infarction ( )
Neuroblastoma ( )
Non-insulin dependent diabetes ( )
Progressive supranuclear palsy ( )
UniProt ID
P3C2G_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2WWE
EC Number
2.7.1.137; 2.7.1.154
Pfam ID
PF00168 ; PF00454 ; PF00792 ; PF00794 ; PF00613 ; PF00787
Sequence
MAYSWQTDPNPNESHEKQYEHQEFLFVNQPHSSSQVSLGFDQIVDEISGKIPHYESEIDE
NTFFVPTAPKWDSTGHSLNEAHQISLNEFTSKSRELSWHQVSKAPAIGFSPSVLPKPQNT
NKECSWGSPIGKHHGADDSRFSILAPSFTSLDKINLEKELENENHNYHIGFESSIPPTNS
SFSSDFMPKEENKRSGHVNIVEPSLMLLKGSLQPGMWESTWQKNIESIGCSIQLVEVPQS
SNTSLASFCNKVKKIRERYHAADVNFNSGKIWSTTTAFPYQLFSKTKFNIHIFIDNSTQP
LHFMPCANYLVKDLIAEILHFCTNDQLLPKDHILSVCGSEEFLQNDHCLGSHKMFQKDKS
VIQLHLQKSREAPGKLSRKHEEDHSQFYLNQLLEFMHIWKVSRQCLLTLIRKYDFHLKYL
LKTQENVYNIIEEVKKICSVLGCVETKQITDAVNELSLILQRKGENFYQSSETSAKGLIE
KVTTELSTSIYQLINVYCNSFYADFQPVNVPRCTSYLNPGLPSHLSFTVYAAHNIPETWV
HSYKAFSFTCWLTYAGKKLCQVRNYRNIPDKKLFFFLVNWNETINFPLEIKSLPRESMLT
VKLFGIACATNNANLLAWTCLPLFPKEKSILGSMLFSMTLQSEPPVEMITPGVWDVSQPS
PVTLQIDFPATGWEYMKPDSEENRSNLEEPLKECIKHIARLSQKQTPLLLSEEKKRYLWF
YRFYCNNENCSLPLVLGSAPGWDERTVSEMHTILRRWTFSQPLEALGLLTSSFPDQEIRK
VAVQQLDNLLNDELLEYLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQVAHRLYWLLKNA
ENEAYFKSWYQKLLAALQFCAGKALNDEFSKEQKLIKILGDIGERVKSASDHQRQEVLKK
EIGRLEEFFQDVNTCHLPLNPALCIKGIDHDACSYFTSNALPLKITFINANPMGKNISII
FKAGDDLRQDMLVLQLIQVMDNIWLQEGLDMQMIIYRCLSTGKDQGLVQMVPDAVTLAKI
HRHSGLIGPLKENTIKKWFSQHNHLKADYEKALRNFFYSCAGWCVVTFILGVCDRHNDNI
MLTKSGHMFHIDFGKFLGHAQTFGGIKRDRAPFIFTSEMEYFITEGGKNPQHFQDFVELC
CRAYNIIRKHSQLLLNLLEMMLYAGLPELSGIQDLKYVYNNLRPQDTDLEATSHFTKKIK
ESLECFPVKLNNLIHTLAQMSAISPAKSTSQTFPQESCLLSTTRSIERATILGFSKKSSN
LYLIQVTHSNNETSLTEKSFEQFSKLHSQLQKQFASLTLPEFPHWWHLPFTNSDHRRFRD
LNHYMEQILNVSHEVTNSDCVLSFFLSEAVQQTVEESSPVYLGEKFPDKKPKVQLVISYE
DVKLTILVKHMKNIHLPDGSAPSAHVEFYLLPYPSEVRRRKTKSVPKCTDPTYNEIVVYD
EVTELQGHVLMLIVKSKTVFVGAINIRLCSVPLDKEKWYPLGNSII
Function Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. May play a role in SDF1A-stimulated chemotaxis.
Tissue Specificity Highly expressed in liver, prostate and testis. Lower levels in small intestine, kidney and pancreas.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
Phosphatidylinositol sig.ling system (hsa04070 )
Salmonella infection (hsa05132 )
Reactome Pathway
Synthesis of PIPs at the Golgi membrane (R-HSA-1660514 )
Synthesis of PIPs at the plasma membrane (R-HSA-1660499 )
BioCyc Pathway
MetaCyc:HS06583-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Genetic Variation [1]
Hyperlipidemia DIS61J3S Strong Biomarker [2]
Myocardial infarction DIS655KI Strong Genetic Variation [2]
Neuroblastoma DISVZBI4 Strong Genetic Variation [1]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [3]
Progressive supranuclear palsy DISO5KRQ moderate Genetic Variation [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G). [5]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G). [11]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G). [7]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G). [9]
Nefazodone DM4ZS8M Approved Nefazodone decreases the expression of Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G). [10]
Atazanavir DMSYRBX Approved Atazanavir decreases the expression of Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G). [10]
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References

1 Analyses of FGFR3 and PIK3CA mutations in neuroblastomas and the effects of the corresponding inhibitors on neuroblastoma cell lines.Int J Oncol. 2019 Dec;55(6):1372-1384. doi: 10.3892/ijo.2019.4896. Epub 2019 Oct 7.
2 Genetic copy number variants in myocardial infarction patients with hyperlipidemia.BMC Genomics. 2011 Nov 30;12 Suppl 3(Suppl 3):S23. doi: 10.1186/1471-2164-12-S3-S23. Epub 2011 Nov 30.
3 First genome-wide association study in an Australian aboriginal population provides insights into genetic risk factors for body mass index and type 2 diabetes.PLoS One. 2015 Mar 11;10(3):e0119333. doi: 10.1371/journal.pone.0119333. eCollection 2015.
4 Variation at the TRIM11 locus modifies progressive supranuclear palsy phenotype.Ann Neurol. 2018 Oct;84(4):485-496. doi: 10.1002/ana.25308. Epub 2018 Sep 15.
5 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
7 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
9 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
10 Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
11 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.